BL-B01D1 is a potentially first-in-class ADC comprised of an EGFR x HER3 bispecific antibody attached to a novel topoisomerase I inhibitor payload (Ed-04) via a tetrapeptide-based cleavable linker. It is being jointly developed by SystImmune (Sichuan Biokin Pharma is the parent company) and Bristol Myers Squibb under an exclusive license and collaboration agreement. Safety and efficacy data from a Phase I study evaluating BL-B01D1 in patients with locally advanced or metastatic urothelial carcinoma were presented as a Proffered paper session.

As of April 29, 2024, 32 urothelial carcinoma patients were enrolled in the Q3W treatment schedule of BL-B01D1, with 29 patients treated at 2.2 mg/kg, two patients at 2.5mg/kg, and three patients at 2.75 mg/kg. Among 23 patients dosed at 2.2 mg/kg evaluable for efficacy, the overall response rate (ORR) was 43.5%, confirmed ORR was 34.8%, and the disease control rate (DCR) was 91.3%, with a median progression-free survival (PFS) of 5.5 months. In patients pretreated with one line of chemotherapy, the ORR was 90%, the confirmed ORR was 80%, and the median PFS was not reached. 

Common treatment-related adverse events (TRAEs) at 2.2 mg/kg included anemia (74%), leukopenia (65%), and thrombocytopenia (65%), with no cases of interstitial lung disease (ILD) reported and no new safety signals observed. These data support the continued conviction that BL-B01D1 has a manageable safety profile and add to the body of evidence that shows encouraging signals of efficacy across a wide variety of tumors. 

KOL insights

" Very interesting new compound but patients did not get prior EVP.  Stronger activity in 2nd line was observed.”- Senior Investigator/ Patient Advocate

“This is exciting data as targeted therapies for UC are evolving fast”- Medical Oncologist

Conclusion 

BL-B01D1’s dual targeting of EGFR and HER3 represents a novel approach, potentially overcoming resistance mechanisms associated with single-target therapies. Both EGFR and HER3 are implicated in urothelial carcinoma pathogenesis, making them attractive targets for combined inhibition. Results presented from the Phase I trial of BL-B01D1 at the ESMO 2024 conference showed that in patients with heavily pretreated urothelial cancer, the drug demonstrated manageable safety with encouraging antitumor activity. Further evaluation of BL-B01D1 in this patient population is ongoing.

Antibody-drug conjugates (ADCs) targeting single antigens like PADCEV, which targets Nectin-4, and TRODELVY, which targets TROP-2, are already approved for urothelial carcinoma, with PADCEV taking the lead following its 2023 approval for first-line treatment alongside KEYTRUDA. The emergence of bispecific ADCs, such as BL-B01D1, is advancing the field of targeted therapies, distinguishing it within the ADC landscape. This positions BL-B01D1 as a versatile treatment option that could meet the unmet needs of patients with limited options, expanding the possibilities in urothelial carcinoma therapy.

For more insight into the patient's burden/epidemiology, treatment, and changing market landscape-related advancements, refer to the:

• Urothelial Carcinoma Market Insight, Epidemiology and Market Forecast - 2034 report.
• Antibody Drug Conjugates- Market Size, Target Population, Competitive Landscape & Market Forecast - 2034  report